The pathogenesis of Graves' disease.

The abnormally increased thyroid activity that is characteristic of Graves' disease is caused by immunoglobulins which specifically interact with the thyroid cell and stimulate it. Increases and decreases in thyroid activity in Graves' disease can be clearly related to rise and fall of these immunoglobulin-mediated activities. The level of immunoglobulin stimulatory activity can be used for prediction of the likelihood of neonatal Graves' disease and of recurrence of disease after cessation of treatment with antithyroid drugs. Investigation of patients with Graves' disease and their families has led to identification of particular human leukocyte antigens and genetically linked markers on immunoglobulins which both appear to incur increased susceptibility to certain autoimmune diseases. Differences in immune function, when compared with control populations, have been found in patients with these genetically linked markers. Protection against autoimmune disease is maintained by purposeful inhibition of any self-directed activity within each function of the immune system and by the controlling interaction of other immune functions. No single deficiency of immune function can be selected as giving the major risk of autoimmune disease, but rather a sum of relative defects resulting in an increased risk. In some patients with Graves' disease the self-protection mechanisms regain sufficient control of the immune functions to reduce the activity of the autoimmune disease, and the patient may achieve clinical remission. Often, however, there is evidence that abnormal immune activity directed against thyroid tissue has persisted with liability to recurrence of the Graves' disease.